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Background: Recent research has attempted to elucidate the relationship between blood-based biomarkers (e.g., endocannabinoids; eCBs: including N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) and mental health outcomes in psychiatric populations such as posttraumatic stress disorder (PTSD). Prior research suggests that adults with PTSD may have altered circulating eCB tone and a blunted mobilization of eCBs (particularly 2-AG) in response to stress (e.g., aerobic exercise), although our understanding has been limited in part due to heterogenous samples and small sample sizes., Methods: A subset of data was pooled from five studies in which women with and without PTSD (N = 98) completed questionnaires related to mood states and a blood draw prior to and following a bout of moderate-intensity aerobic exercise in order to determine: 1) whether circulating eCBs differ between groups and whether depressive and PTSD symptom severity are associated with baseline eCBs, 2) whether a bout of aerobic exercise increases circulating eCBs in adult women with PTSD, and 3) whether circulating eCBs are associated with overall mood states and exercise-induced improvements in mood states in women with and without PTSD., Results: PTSD diagnoses were not associated with baseline concentrations of eCBs. Greater depressive symptom severity and PTSD symptom severity within the negative alteration in cognition and mood cluster were associated with lower circulating AEA. Circulating AEA significantly increased following aerobic exercise for both groups, whereas circulating 2-AG only increased in women without PTSD. Greater circulating AEA within the PTSD group was associated with lower depressive mood, confusion, and total mood disturbance., Conclusions: These findings suggest that greater circulating AEA is associated with better overall mood and lower depressive and PTSD symptom severity, and that an acute bout of moderate-intensity aerobic exercise increases circulating AEA (but not 2-AG) in adult women with PTSD. These findings are consistent with the idea that greater eCB tone (particularly AEA) following pharmacological and/or non-pharmacological manipulations may be beneficial for improving psychological outcomes (e.g., mood, cognition) among PTSD, and possibly other psychiatric populations., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: We recently demonstrated that moderate-intensity aerobic exercise delivered during the consolidation of fear extinction learning reduced threat expectancy during a test of extinction recall among women with posttraumatic stress disorder (PTSD). These findings suggest that exercise may be a potential candidate for improving the efficacy of exposure-based therapies, which are hypothesized to work via the mechanisms of fear extinction learning. The purpose of this secondary analysis was to examine whether exercise-induced increases in circulating concentrations of candidate biomarkers: endocannabinoids (anandamide [AEA]; 2-arachidonoylglycerol [2-AG], brain-derived neurotrophic factor (BDNF), and homovanillic acid (HVA), mediate the effects of exercise on extinction recall., Methods: Participants (N = 35) completed a 3-day fear acquisition (day 1), extinction (day 2), and extinction recall (day 3) protocol, in which participants were randomly assigned to complete either moderate-intensity aerobic exercise (EX) or a light-intensity control (CON) condition following extinction training (day 2). Blood was obtained prior to and following EX or CON. Threat expectancy ratings during tests of extinction recall (i.e., initial fear recall and fear recall following reinstatement) were obtained 24 h following EX or CON. Mediation was tested using linear-mixed effects models and bootstrapping of the indirect effect., Results: Circulating concentrations of AEA and BDNF (but not 2-AG and HVA) were found to mediate the relationship between moderate-intensity aerobic exercise and reduced threat expectancy ratings following reinstatement (AEA 95% CI: -0.623 to -0.005; BDNF 95% CI: -0.941 to -0.005)., Conclusions: Exercise-induced increases in peripheral AEA and BDNF appear to play a role in enhancing consolidation of fear extinction learning, thereby leading to reduced threat expectancies following reinstatement among women with PTSD. Future mechanistic research examining these and other biomarkers (e.g., brain-based biomarkers) is warranted., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Exercise has been examined as an adjunctive treatment for substance use disorders (SUDs), yet few exercise interventions have been conducted among patients undergoing intensive outpatient (IOP) treatment, who may be the most vulnerable to relapse and for whom exercise could provide the most benefits. This study examined the effects of aerobic exercise, in addition to IOP treatment, on psychological variables and endocannabinoids in individuals with SUDs. Methods : Twenty-one SUD patients (mean age 35 years) were recruited from local IOPs. Participants were randomized to either treatment-as-usual (TAU, at their outpatient clinic) or TAU plus aerobic exercise training (EX). EX participants engaged in supervised, moderate-intensity exercise for 30 min, 3 times/week for 6 weeks. TAU participants came into the laboratory once per week for assessments and a 30-min quiet rest session. Participants provided blood samples and completed questionnaires evaluating substance use, mood states, depression, anxiety, perceived stress, self-efficacy to abstain from substance use, and craving. Data were analyzed with Mann-Whitney U tests or mixed model ANOVAs to determine group differences in outcomes acutely and over 6 weeks. Results : Over 6 weeks, there were reductions in perceived stress ( p  < 0.01) and craving ( p  < 0.05) for both groups. There were no group differences in abstinence rates or changes from baseline in self-efficacy, depression, or anxiety ( p  > 0.05). Acutely, both exercise and quiet rest sessions led to reductions in craving, tension, depression, anger, confusion, and total mood disturbance (all p s < 0.05). In addition, the EX group experienced acute increases in vigor and circulating concentrations of the endocannabinoid, anandamide ( p  < 0.01). Conclusions : An adjunctive aerobic exercise program during SUD treatment was associated with similar reductions in perceived stress and drug craving as standard care. Thirty minutes of exercise or quiet rest led to acute improvements in mood, but exercise produced the additional benefit of increases in vigor and circulating anandamide.

The endocannabinoid (eCB) system is implicated in the pathophysiology of depression and is responsive to acute exercise in healthy adults., Purpose: We aimed to describe acute changes in serum eCB across a prescribed moderate (MOD) and a self-selected/preferred (PREF) intensity exercise session in women with major depressive disorder (MDD) and determine relationships between changes in eCB and mood states., Methods: Women with MDD (n = 17) exercised in separate sessions for 20 min on a cycle ergometer at both MOD or PREF in a within-subjects design. Blood was drawn before and within 10 min after exercise. Serum concentrations of eCB (anandamide [AEA], 2-arachidonoylglycerol) and related lipids (palmitoylethanolamine, oleoylethanolamine, 2-oleoylglycerol) were quantified using stable isotope-dilution, liquid chromatography/mass spectrometry/mass spectrometry. The profile of mood states and state-trait anxiety inventory (state only) were completed before, 10 min and 30 min postexercise., Results: Significant elevations in AEA (P = 0.013) and oleoylethanolamine (P = 0.024) occurred for MOD (moderate effect sizes: Cohen's d = 0.58 and 0.41, respectively). Significant (P < 0.05) moderate negative associations existed between changes in AEA and mood states for MOD at 10 min (depression, confusion, fatigue, total mood disturbance [TMD] and state anxiety) and 30 min postexercise (confusion, TMD and state anxiety). Significant (P < 0.05) moderate negative associations existed between 2-arachidonoylglycerol and mood states at 10 min (depression and confusion) and 30 min postexercise (confusion and TMD). Changes in eCB or related lipids or eCB-mood relationships were not found for PREF., Conclusion: Given the broad, moderate-strength relationships between improvements in mood states and eCB increases after MOD, it is plausible that the eCB system contributes to the mood-enhancing effects of prescribed acute exercise in MDD. Alternative mechanisms are likely involved in the positive mood state effects of preferred exercise.

The endocannabinoid (eCB) system is a modulatory system that is both altered by stress and mediates the effects of acute stress, including contributing to restoration of homeostasis. Earlier studies suggest that circulating eCBs are dysregulated in adults with post-traumatic stress disorder (PTSD); however, it is not known whether circulating eCBs remain responsive to stress. The purpose of this study was to examine eCB and psychological responses to physical (exercise) and psychosocial (Trier Social Stress Test) stressors, using a randomized, counterbalanced procedure in adults with PTSD and healthy controls (N = 20, mean age = 24, SD = 7 yrs). Results from mixed-design, repeated measures ANOVAs revealed significant increases (p <  .05) in N-arachidonoylethanolamine (AEA) and oleoylethanolamide (OEA) following exercise and psychosocial stress in both groups. However, only the control group exhibited a significant increase (p < .05) in 2-arachidonoylglycerol (2-AG) following exercise and psychosocial stress exposure. These data extend our current understanding of circulating eCB responsiveness in PTSD, and provide preliminary evidence to suggest that the eCB system is hypoactive in PTSD following exposure to physical and psychosocial stressors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Previous reports have shown improvements in mood and increases in endocannabinoids in healthy adults following a session of aerobic exercise, but it is unclear whether adults with posttraumatic stress disorder (PTSD) experience similar responses. The purpose of this study was to examine psychobiological responses (plasma endocannabinoids [eCBs], mood, and pain) to aerobic exercise in a sample of adults with a diagnosis of PTSD (n = 12) and healthy controls (n = 12). Participants engaged in an aerobic exercise session in which they ran on a treadmill for 30 min at a moderate intensity (70 to 75% maximum heart rate [MHR]). Results indicated improvements in mood states and reductions in pain for both groups following exercise, ds = 0.19 to 1.53. Circulating concentrations of N-arachidonylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), and oleoylethanolamide (OEA) significantly increased (ps = .000 to .050) following the aerobic exercise session for both groups. There were no significant time, group, or interaction effects (ps = .062 to .846) for palmitoylethanolamide (PEA) and 2-oleoylglycerol (2-OG). Although eCBs increased significantly for both groups, within-group effect size calculations indicated the healthy controls experienced a greater magnitude of change for AEA when compared with adults with PTSD, d = 1.21 and d = 0.45, respectively; as well as for 2-AG, d = 0.43 and d = 0.21, respectively. The findings from this study indicated that adults with and without PTSD reported significant mood improvements following 30 min of moderate-intensity aerobic exercise. In addition, the endocannabinoid system was activated in adults with and without PTSD, although effect sizes suggest that adults with PTSD may have a blunted endocannabinoid response to exercise., (Copyright © 2018 International Society for Traumatic Stress Studies.)

Objective: The purpose of this study was to examine the interaction between the endogenous opioid and endocannabinoid (eCB) systems in a pain modulatory process known as exercise-induced hypoalgesia (EIH)., Design: Randomized controlled trial., Setting: Clinical research unit in a hospital., Subjects: Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study., Methods: Participants were administered (randomized, double-blind, counterbalanced procedure) an opioid antagonist (i.e., naltrexone) and a placebo prior to performing pain testing and isometric exercise., Results: Results indicated that 2-arachidonoylglycerol (2-AG) and 2-oleoylglycerol (2-OG) increased significantly (P < 0.05) following exercise in both placebo and naltrexone conditions. In comparison, N-arachidonylethanolamine (AEA) and oleoylethanolamine (OEA) increased significantly (P < 0.05) following exercise in the placebo condition but not the naltrexone condition. There were no significant (P > 0.05) differences in palmitolethanolamine (PEA) between the placebo and naltrexone conditions., Conclusions: As reductions in pain (i.e., EIH) were observed following both conditions, these results suggest that the opioid system may not be the primary system involved in exercise-induced hypoalgesia and that 2-AG and 2-OG could contribute to nonopioid exercise-induced hypoalgesia. Moreover, as exercise-induced increases in AEA and OEA were blocked by naltrexone pretreatment, this suggests that the opioid system may be involved in the increase of AEA and OEA following exercise., (© 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Acute aerobic exercise improves mood and activates the endocannabinoid (eCB) system in physically active individuals; however, both mood and eCB responses to exercise may vary based on habitual levels of physical activity., Purpose: This study aimed to examine eCB and mood responses to prescribed and preferred exercises among individuals with low, moderate, and high levels of physical activity., Methods: Thirty-six healthy adults (21 ± 4 yr) were recruited from low (≤60 min moderate-vigorous physical activity [MVPA] per week), moderate (150-299 min MVPA per week), and high (≥300 MVPA per week) physical activity groups. Participants performed both prescribed (approximately 70%-75% max) and preferred (i.e., self-selected) aerobic exercise on separate days. Mood states and eCB concentrations were assessed before and after exercise conditions., Results: Both preferred and prescribed exercise resulted in significant increases (P < 0.01) in circulating eCB (N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol); however, increases in AEA (P < 0.05) were larger in the prescribed condition. Likewise, both preferred and prescribed exercise elicited positive mood improvements compared with preexercise values, but changes in state anxiety, total mood disturbance, and confusion were greater in the preferred condition (P < 0.05). Changes in 2-arachidonoylglycerol concentrations were found to negatively correlate with changes in depression, tension, and total mood disturbance in the preferred condition (P < 0.05), and changes in AEA were positively associated with changes in vigor in the prescribed condition (P < 0.05). There were no significant group differences for mood or eCB outcomes., Conclusion: These results indicate that eCB and mood responses to exercise do not differ significantly between samples with varying physical activity levels. This study also demonstrates that in addition to prescribed exercise, preferred exercise activates the eCB system, and this activation may contribute to positive mood outcomes with exercise.

Background: Despite cannabis being the most widely used illicit substance in the United States, individuals diagnosed with cannabis use disorder (CUD) have few well-researched, affordable treatment options available to them. Although found to be effective for improving treatment outcomes in other drug populations, exercise is an affordable and highly accessible treatment approach that has not been routinely investigated in cannabis users., Objectives: The aim of this paper is to inform the topic regarding exercise's potential as an adjunctive treatment for individuals with CUD., Methods: We reviewed the evidence surrounding cannabis use and its current treatment in the United States, explored the rationale for including exercise in the treatment of substance use disorders (SUDs), and in particular, proposed a biological mechanism (i.e., endocannabinoids (eCBs)) that should be examined when utilizing exercise for the treatment of CUD., Results: Cannabis use is widespread and increasing in the United States. Chronic, heavy cannabis use may dysregulate the endogenous cannabinoid system, which has implications for several psychobiological processes that interact with the eCB system such as reward processing and the stress response. Given that exercise is a potent activator of the eCB system, it is mechanistically plausible that exercise could be an optimal method to supplement cessation efforts by reducing psychophysical withdrawal, managing stress, and attenuating drug cravings., Conclusion: We suggest there is a strong behavioral and physiological rationale to design studies which specifically assess the efficacy of exercise, in combination with other therapies, in treating CUD. Moreover, it will be especially important to include the investigation of psychobiological mechanisms (e.g., eCBs, hippocampal volume), which have been associated with both exercise and SUDs, to examine the broader impact of exercise on behavioral and physiological responses to treatment.